Passing the Chemical Sniff Test

How innovative 3D models of the human airway tract can help chemical manufacturers reduce their reliance on animal models. The next installment in our Chemical Attractions series.

We live in a chemical world—tons of it are produced every day. Agricultural chemicals, food additives, pharmaceuticals, fuels for power production, chemical consumer products are all part of the tens of thousands of chemicals on the market.

For sure, chemicals improve the quality of our lives. Plant protection products in the form of pesticides and fertilizers increase food production and carbon fibers can be used in the manufacture of new lightweight materials. Ceramic fibers can be used as insulation materials and have frequently been used as a replacement for asbestos. Acrylic adhesives, superglue and environmentally safe biodegradable plastics are other examples of how chemicals contribute to daily life.

The European Chemicals Agency (ECHA) and the US Environmental Protection Agency (EPA) generally require in vivo safety data to register a chemical product.

Regulatory authorities and companies are considering different ways of testing particularly using 3Rs principles especially by replacing the use of live animals. To meet these objectives, toxicologists are developing intelligent testing strategies based on human tissues or models derived from human tissues.

In Vitro Inhalation Tests

One innovation method that regulatory agencies have begun looking at are 3D models of the human airway tract, which studies show can help us to predict responses to the chemical products in vivo. Such models recapitulate the typical characteristics of our own breathing environment, such as the tight junction proteins, ciliated cells, basal cells and mucous traps that make up the airway epithelium. One is able to observe cells that form the front line of defense against respiratory toxins with much greater resolution, and, in our case, identify specific liabilities that indicate a high risk of airway toxicity or predict a nontoxic starting dose for in vivo studies.

Charles River currently use two 3D human-derived reconstructed airway tissue models (EpiAirwayTM and MucilAirTM) for measuring toxicity or assessing efficacy of inhalable chemicals. Using these 3D tissue models, we have identified, tested and used specific markers of toxicity associated with epithelial damage. These human tissue models have been used in support of our 3Rs program by helping us to design better animal inhalation toxicology tests or as replacement of the animal tests in occupational toxicology risk assessments.

Inhalation toxicology tests have applications across a broad swathe of chemicals. They could be useful in any situation where the chemical is sprayed—like an agrochemical being used for pest control, industrial solvents that act as carriers for surface coatings such as paints, varnishes and adhesives, and even pharmaceutical manufacturing facilities where particles from the powders used to make the drugs can escape into the air. They could help us to identify how exposure to these particles, materials and gases impact the upper airway tract.

Importantly, 3D tissue cultures might also help assess the clearance of nanoparticles released in the environment. Nanoparticles are already contained in many consumer products, including next-generation batteries, pharmaceuticals and next-generation solar cells. While the inclusion of nanomaterials can enhance their performance of a product, the breakdown of these products at the end of their useful life they can end up in landfills or wastewater treatment facilities.

Though in vivo tests are still the norm, regulatory authorities are interested in the data generated by 3D tissue models as we continue to understand how they can be used to replace the animal tests.These, and other tests, are being used in support of our 3Rs commitments.

Should these in vitro techniques become accepted by regulators, they could be a real game changer. Indeed, given that we should all be striving to reduce our reliance on in vivo models in any way possible, leveraging the expertise of in vitro toxicologists to push forward with innovative alternatives should be the preferred option.